1. Technical Field
A device and method for use in the field of chemical testing is disclosed. More particularly, the device can be used for filtering whole blood for testing on an integrated circuit.
2. Summary of the Related Art
Point-of-Care (POC) diagnostic medical devices facilitate early stage detection of diseases, enable more individually tailored therapies, and allow doctors to follow up with patients more easily to see if prescribed treatments are working. To ensure widespread adoption, these tools must be accurate, easy to use by untrained individuals, and inexpensive to produce and distribute. Immuno-Assay (IA) applications are particularly well-suited for the POC since a wide range of conditions, from cardiovascular disease to cancer to communicable infections, can be identified from soluble protein bio-markers. The detection and quantitation of these bio-markers from raw samples such as whole blood often involves labeling the target protein using fluorescent or phosphorescent molecules, enzymes, quantum dots, metal particles or magnetic particles. For high sensitivity applications, the labels specifically bound to the target analytes must be distinguished from the unbound ones that contribute to background noise. By combining both label separation and detection in a low cost, easy to use format, the Immuno-Chromatographic Test (ICT) achieves stand-alone operation, i.e. the ability to perform an assay without necessitating a secondary device like an electronic reader or an external sample preparation system. Stand-alone operation is an often overlooked attribute, but one that is key to the popularity of ICTs, achieved despite other drawbacks such as low biochemical sensitivity, user interpretation, inaccurate quantitation, timing requirements, and awkward multiplexing.
The use of magnetic particle labeling is ideal for POC applications; magnetic particles can be individually detected, so sub-pico molar sensitivities can be achieved without signal amplification steps that can take up to an hour as in case of enzymatic labeling. Also, by micro-arraying the sensor areas onto which the particles bind, multiplexed operation can be achieved at low cost. The use of magnetic particles can reduce incubation times, since they can bind to the target analytes with solution-phase kinetics due to their high surface area to volume ratio. Furthermore, the ability to pull the magnetic particles out of solution magnetically and gravitationally overcomes the slow diffusion processes that plague most high sensitivity protocols. The signals from magnetic particles can be stable over time, insensitive to changes in temperature or chemistries and detected in opaque or translucent solutions like whole blood or plasma. The biological magnetic background signal can be low, so high assay sensitivity can be achieved with minimal sample preparation. Most importantly, the use of magnetic particles as assay labels can permit stand-alone device operation, since these particles can be both manipulated and detected electromagnetically.
“Magnetic particles” are typically nano-meter or micro-meter sized particles that display magnetic, diamagnetic, ferromagnetic, ferrimagnetic, paramagnetic, super-paramagnetic or antiferromagnetic behavior. “Magnetic particles” can refer to individual particles or larger aggregates of particles such as magnetic beads.
ICTs in which magnetic particles are used as the assay labels are an improvement to conventional ICTs since the detection of the particles is not limited to the surface of the strip, but can be performed throughout the volume of the strip, resulting in higher sensitivities and improved quantitative accuracy. However, volumetric detection of magnetic particles cannot be readily integrated in a stand-alone device, so these implementations require an external device to measure the volume magnetization in the strip.
One alternative for integration into a stand-alone device is to use magnetic particles that bind to the target analytes in solution before sedimenting via gravity or magnetic force to sensor areas where the specifically bound particles can be detected. A bio-functionalized IC can be used to detect the specifically bound particles. However, most IC-based immuno-assay implementations reported to date cannot operate stand-alone since they require either off-chip components for particle detection, or micro-fluidic actuation for particle manipulation and sample preparation. Other implementations simply cannot reach the cost structures necessary to compete in the current marketplace.
For POC application, it is desirable that the sample preparation be rapid since the assay is limited to 10-15 minutes. In addition, to obviate the need for refrigeration equipment and to facilitate storage and distribution, a dry sample preparation system is desired. It is also desirable to have a sample preparation system that receives small unprocessed samples from patients. The average hanging drop of blood from a finger stick yields approximately 15 μl of fluid. For more fluid, a complicated venu-puncture can be necessary. Moreover, the sample preparation system must be low-cost since biological contamination concerns dictate that all material in contact with biological samples be discarded. It is also desirable that the sample preparation system be amenable to multiplexed operation.